HRP980356A2 - Prostaglandin agonists - Google Patents

Info

Publication number

HRP980356A2

HRP980356A2 HR60/050,575A HRP980356A HRP980356A2 HR P980356 A2 HRP980356 A2 HR P980356A2 HR P980356 A HRP980356 A HR P980356A HR P980356 A2 HRP980356 A2 HR P980356A2

Authority

HR

Croatia

Prior art keywords

pharmaceutically acceptable

phenyl

compound according

hydroxy

acceptable salts

Prior art date

1997-06-23

Links

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• 150000003180 prostaglandins Chemical class 0.000 title claims description 28
• 239000000556 agonist Substances 0.000 title description 56
• 150000001875 compounds Chemical class 0.000 claims description 447
• 150000003839 salts Chemical class 0.000 claims description 196
• 210000000988 bone and bone Anatomy 0.000 claims description 178
• -1 propylene, propenylene Chemical group 0.000 claims description 156
• 238000000034 method Methods 0.000 claims description 108
• 239000000651 prodrug Substances 0.000 claims description 92
• 229940002612 prodrug Drugs 0.000 claims description 92
• 208000001132 Osteoporosis Diseases 0.000 claims description 85
• 241000124008 Mammalia Species 0.000 claims description 76
• 229920006395 saturated elastomer Polymers 0.000 claims description 68
• 208000010392 Bone Fractures Diseases 0.000 claims description 59
• 229910052757 nitrogen Chemical group 0.000 claims description 53
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 46
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 43
• 239000008194 pharmaceutical composition Substances 0.000 claims description 43
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 40
• 125000001424 substituent group Chemical group 0.000 claims description 39
• 239000003795 chemical substances by application Substances 0.000 claims description 38
• 206010065687 Bone loss Diseases 0.000 claims description 34
• 125000005842 heteroatom Chemical group 0.000 claims description 33
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 31
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 31
• 229910052760 oxygen Inorganic materials 0.000 claims description 31
• 239000001301 oxygen Substances 0.000 claims description 31
• 229910052717 sulfur Inorganic materials 0.000 claims description 31
• 239000011593 sulfur Chemical group 0.000 claims description 31
• 239000003937 drug carrier Substances 0.000 claims description 30
• 229910052799 carbon Inorganic materials 0.000 claims description 28
• 229940124325 anabolic agent Drugs 0.000 claims description 27
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 27
• 239000003263 anabolic agent Substances 0.000 claims description 25
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 24
• 125000005843 halogen group Chemical group 0.000 claims description 24
• 230000000123 anti-resoprtive effect Effects 0.000 claims description 23
• 125000003831 tetrazolyl group Chemical group 0.000 claims description 23
• 239000000199 parathyroid hormone Substances 0.000 claims description 22
• PUZPDOWCWNUUKD-UHFFFAOYSA-M sodium fluoride Chemical compound [F-].[Na+] PUZPDOWCWNUUKD-UHFFFAOYSA-M 0.000 claims description 22
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 20
• 125000002619 bicyclic group Chemical group 0.000 claims description 19
• 230000001965 increasing effect Effects 0.000 claims description 19
• 210000000689 upper leg Anatomy 0.000 claims description 19
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 18
• 239000000122 growth hormone Substances 0.000 claims description 18
• 125000004076 pyridyl group Chemical group 0.000 claims description 18
• 125000003545 alkoxy group Chemical group 0.000 claims description 17
• 125000000335 thiazolyl group Chemical group 0.000 claims description 17
• 102000003982 Parathyroid hormone Human genes 0.000 claims description 16
• 108090000445 Parathyroid hormone Proteins 0.000 claims description 16
• 229960001319 parathyroid hormone Drugs 0.000 claims description 16
• 125000002947 alkylene group Chemical group 0.000 claims description 15
• 125000003342 alkenyl group Chemical group 0.000 claims description 14
• 125000000217 alkyl group Chemical group 0.000 claims description 14
• 125000005678 ethenylene group Chemical group [H]C([*:1])=C([H])[*:2] 0.000 claims description 14
• 230000002829 reductive effect Effects 0.000 claims description 14
• 239000002552 dosage form Substances 0.000 claims description 13
• 230000035876 healing Effects 0.000 claims description 13
• 108010051696 Growth Hormone Proteins 0.000 claims description 12
• NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 claims description 12
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 12
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 11
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 11
• 239000011775 sodium fluoride Substances 0.000 claims description 11
• 235000013024 sodium fluoride Nutrition 0.000 claims description 11
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 11
• 229910052739 hydrogen Inorganic materials 0.000 claims description 10
• 125000004043 oxo group Chemical group O=* 0.000 claims description 10
• 201000001245 periodontitis Diseases 0.000 claims description 10
• 239000002522 prostaglandin receptor stimulating agent Substances 0.000 claims description 10
• 125000001544 thienyl group Chemical group 0.000 claims description 10
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 9
• 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 9
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 9
• ZQZFYGIXNQKOAV-OCEACIFDSA-N Droloxifene Chemical group C=1C=CC=CC=1C(/CC)=C(C=1C=C(O)C=CC=1)\C1=CC=C(OCCN(C)C)C=C1 ZQZFYGIXNQKOAV-OCEACIFDSA-N 0.000 claims description 9
• HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 claims description 9
• 239000000460 chlorine Substances 0.000 claims description 9
• 229950004203 droloxifene Drugs 0.000 claims description 9
• 229960002897 heparin Drugs 0.000 claims description 9
• 229920000669 heparin Polymers 0.000 claims description 9
• 239000001257 hydrogen Substances 0.000 claims description 9
• 125000004504 1,2,4-oxadiazolyl group Chemical group 0.000 claims description 8
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
• 125000004450 alkenylene group Chemical group 0.000 claims description 8
• 230000028327 secretion Effects 0.000 claims description 8
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 8
• 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims description 7
• 125000004738 (C1-C6) alkyl sulfinyl group Chemical group 0.000 claims description 7
• 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 7
• 125000006701 (C1-C7) alkyl group Chemical group 0.000 claims description 7
• 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 7
• HMBSMLATJKWAHH-UHFFFAOYSA-N 2-phenyl-1-[4-(2-pyrrolidin-1-ylethoxy)phenyl]-3,4-dihydro-1h-isoquinolin-6-ol Chemical compound C1CC2=CC(O)=CC=C2C(C=2C=CC(OCCN3CCCC3)=CC=2)N1C1=CC=CC=C1 HMBSMLATJKWAHH-UHFFFAOYSA-N 0.000 claims description 7
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 7
• VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical group C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 7
• 239000005977 Ethylene Substances 0.000 claims description 7
• 125000005236 alkanoylamino group Chemical group 0.000 claims description 7
• 125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 7
• 125000003282 alkyl amino group Chemical group 0.000 claims description 7
• 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 7
• 125000005422 alkyl sulfonamido group Chemical group 0.000 claims description 7
• 125000000304 alkynyl group Chemical group 0.000 claims description 7
• 125000006598 aminocarbonylamino group Chemical group 0.000 claims description 7
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 7
• 229910052801 chlorine Inorganic materials 0.000 claims description 7
• 125000001153 fluoro group Chemical group F* 0.000 claims description 7
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 7
• 230000001506 immunosuppresive effect Effects 0.000 claims description 7
• 125000002950 monocyclic group Chemical group 0.000 claims description 7
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 7
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 7
• QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 claims description 7
• 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 7
• 230000002269 spontaneous effect Effects 0.000 claims description 7
• 230000004936 stimulating effect Effects 0.000 claims description 7
• 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims description 7
• 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 claims description 7
• DODQJNMQWMSYGS-QPLCGJKRSA-N 4-[(z)-1-[4-[2-(dimethylamino)ethoxy]phenyl]-1-phenylbut-1-en-2-yl]phenol Chemical compound C=1C=C(O)C=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 DODQJNMQWMSYGS-QPLCGJKRSA-N 0.000 claims description 6
• OGSPWJRAVKPPFI-UHFFFAOYSA-N Alendronic Acid Chemical compound NCCCC(O)(P(O)(O)=O)P(O)(O)=O OGSPWJRAVKPPFI-UHFFFAOYSA-N 0.000 claims description 6
• 239000012634 fragment Substances 0.000 claims description 6
• GZUITABIAKMVPG-UHFFFAOYSA-N raloxifene Chemical compound C1=CC(O)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=C(O)C=C2S1 GZUITABIAKMVPG-UHFFFAOYSA-N 0.000 claims description 6
• 229960004622 raloxifene Drugs 0.000 claims description 6
• 229960001603 tamoxifen Drugs 0.000 claims description 6
• SSQLMQBZAPRIRS-UHFFFAOYSA-N 6-(4-hydroxyphenyl)-5-[[4-(2-piperidin-1-ylethoxy)phenyl]methyl]naphthalen-2-ol Chemical compound C1=CC(O)=CC=C1C1=CC=C(C=C(O)C=C2)C2=C1CC(C=C1)=CC=C1OCCN1CCCCC1 SSQLMQBZAPRIRS-UHFFFAOYSA-N 0.000 claims description 5
• DBVJJBKOTRCVKF-UHFFFAOYSA-N Etidronic acid Chemical compound OP(=O)(O)C(O)(C)P(O)(O)=O DBVJJBKOTRCVKF-UHFFFAOYSA-N 0.000 claims description 5
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 5
• MPBVHIBUJCELCL-UHFFFAOYSA-N Ibandronate Chemical compound CCCCCN(C)CCC(O)(P(O)(O)=O)P(O)(O)=O MPBVHIBUJCELCL-UHFFFAOYSA-N 0.000 claims description 5
• JJKOTMDDZAJTGQ-DQSJHHFOSA-N Idoxifene Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN2CCCC2)=CC=1)/C1=CC=C(I)C=C1 JJKOTMDDZAJTGQ-DQSJHHFOSA-N 0.000 claims description 5
• 201000010814 Synostosis Diseases 0.000 claims description 5
• IUPVFHXEIGLEFF-UHFFFAOYSA-N [4-[2-(3-azabicyclo[2.2.1]heptan-3-yl)ethoxy]phenyl]-[6-hydroxy-2-(4-hydroxyphenyl)-1-benzothiophen-3-yl]methanone Chemical compound C1=CC(O)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3C4CCC(C4)C3)=CC=2)C2=CC=C(O)C=C2S1 IUPVFHXEIGLEFF-UHFFFAOYSA-N 0.000 claims description 5
• 229960002286 clodronic acid Drugs 0.000 claims description 5
• ACSIXWWBWUQEHA-UHFFFAOYSA-N clodronic acid Chemical compound OP(O)(=O)C(Cl)(Cl)P(O)(O)=O ACSIXWWBWUQEHA-UHFFFAOYSA-N 0.000 claims description 5
• 230000001815 facial effect Effects 0.000 claims description 5
• 239000011737 fluorine Substances 0.000 claims description 5
• 229910052731 fluorine Inorganic materials 0.000 claims description 5
• 229960005236 ibandronic acid Drugs 0.000 claims description 5
• 229950002248 idoxifene Drugs 0.000 claims description 5
• 239000002089 prostaglandin antagonist Substances 0.000 claims description 5
• XFCLJVABOIYOMF-QPLCGJKRSA-N toremifene Chemical compound C1=CC(OCCN(C)C)=CC=C1C(\C=1C=CC=CC=1)=C(\CCCl)C1=CC=CC=C1 XFCLJVABOIYOMF-QPLCGJKRSA-N 0.000 claims description 5
• 229960005026 toremifene Drugs 0.000 claims description 5
• KPSLPXFASPKQHV-PXJZQJOASA-N (5r,6s)-6-phenyl-5-[4-(2-piperidin-1-ylethoxy)phenyl]-5,6,7,8-tetrahydronaphthalen-2-ol Chemical compound C1([C@@H]2[C@@H](C3=CC=C(C=C3CC2)O)C=2C=CC(OCCN3CCCCC3)=CC=2)=CC=CC=C1 KPSLPXFASPKQHV-PXJZQJOASA-N 0.000 claims description 4
• 108090000723 Insulin-Like Growth Factor I Proteins 0.000 claims description 4
• 102000004218 Insulin-Like Growth Factor I Human genes 0.000 claims description 4
• IIDJRNMFWXDHID-UHFFFAOYSA-N Risedronic acid Chemical compound OP(=O)(O)C(P(O)(O)=O)(O)CC1=CC=CN=C1 IIDJRNMFWXDHID-UHFFFAOYSA-N 0.000 claims description 4
• DKJJVAGXPKPDRL-UHFFFAOYSA-N Tiludronic acid Chemical group OP(O)(=O)C(P(O)(O)=O)SC1=CC=C(Cl)C=C1 DKJJVAGXPKPDRL-UHFFFAOYSA-N 0.000 claims description 4
• 229960004343 alendronic acid Drugs 0.000 claims description 4
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 4
• 229960004585 etidronic acid Drugs 0.000 claims description 4
• XZEUAXYWNKYKPL-WDYNHAJCSA-N levormeloxifene Chemical compound C1([C@H]2[C@@H](C3=CC=C(C=C3OC2(C)C)OC)C=2C=CC(OCCN3CCCC3)=CC=2)=CC=CC=C1 XZEUAXYWNKYKPL-WDYNHAJCSA-N 0.000 claims description 4
• 229950002728 levormeloxifene Drugs 0.000 claims description 4
• WRUUGTRCQOWXEG-UHFFFAOYSA-N pamidronate Chemical compound NCCC(O)(P(O)(O)=O)P(O)(O)=O WRUUGTRCQOWXEG-UHFFFAOYSA-N 0.000 claims description 4
• 229960003978 pamidronic acid Drugs 0.000 claims description 4
• 229960000759 risedronic acid Drugs 0.000 claims description 4
• 229960005324 tiludronic acid Drugs 0.000 claims description 4
• 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 3
• 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 3
• XFKAGGZZSKXZEF-AEFFLSMTSA-N (2S,3S)-2-[6-(2H-tetrazol-5-yl)hexyl]-3-[2-[3-(trifluoromethyl)phenyl]ethenyl]cyclopentan-1-one Chemical compound FC(C=1C=C(C=CC1)C=C[C@H]1[C@@H](C(CC1)=O)CCCCCCC=1N=NNN1)(F)F XFKAGGZZSKXZEF-AEFFLSMTSA-N 0.000 claims description 2
• LPTKMZBIOILCNM-QAPCUYQASA-N (2S,3S)-3-[2-(3,5-dichlorophenyl)ethenyl]-2-[6-(2H-tetrazol-5-yl)hexyl]cyclopentan-1-one Chemical compound ClC=1C=C(C=C(C1)Cl)C=C[C@H]1[C@@H](C(CC1)=O)CCCCCCC=1N=NNN1 LPTKMZBIOILCNM-QAPCUYQASA-N 0.000 claims description 2
• TTXPKWYWEGVEHO-AEFFLSMTSA-N (2S,3S)-3-[2-(3-chlorophenyl)ethenyl]-2-[6-(2H-tetrazol-5-yl)hexyl]cyclopentan-1-one Chemical compound ClC=1C=C(C=CC1)C=C[C@H]1[C@@H](C(CC1)=O)CCCCCCC=1N=NNN1 TTXPKWYWEGVEHO-AEFFLSMTSA-N 0.000 claims description 2
• TTZDGSOTELRENM-AEFFLSMTSA-N (2S,3S)-3-[2-(4-fluorophenyl)ethenyl]-2-[6-(2H-tetrazol-5-yl)hexyl]cyclopentan-1-one Chemical compound FC1=CC=C(C=C1)C=C[C@H]1[C@@H](C(CC1)=O)CCCCCCC=1N=NNN1 TTZDGSOTELRENM-AEFFLSMTSA-N 0.000 claims description 2
• IVXHJAYZBSJHPL-CVEARBPZSA-N (2S,3S)-3-[2-[4-chloro-3-(trifluoromethyl)phenyl]ethenyl]-2-[6-(2H-tetrazol-5-yl)hexyl]cyclopentan-1-one Chemical compound ClC1=C(C=C(C=C1)C=C[C@H]1[C@@H](C(CC1)=O)CCCCCCC=1N=NNN1)C(F)(F)F IVXHJAYZBSJHPL-CVEARBPZSA-N 0.000 claims description 2
• 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 2
• CVEVGIMIRDODEY-AEFFLSMTSA-N 7-[(1S,5S)-2-oxo-5-[2-[3-(trifluoromethyl)phenyl]ethenyl]cyclopentyl]heptanoic acid Chemical compound O=C1[C@H]([C@@H](CC1)C=CC1=CC(=CC=C1)C(F)(F)F)CCCCCCC(=O)O CVEVGIMIRDODEY-AEFFLSMTSA-N 0.000 claims description 2
• WHWXRSHZPCVNEK-QAPCUYQASA-N 7-[(1s,2s)-2-[2-(3,5-dichlorophenyl)ethenyl]-5-oxocyclopentyl]heptanoic acid Chemical compound C1CC(=O)[C@@H](CCCCCCC(=O)O)[C@@H]1C=CC1=CC(Cl)=CC(Cl)=C1 WHWXRSHZPCVNEK-QAPCUYQASA-N 0.000 claims description 2
• GMKMYYJTNINTPO-AEFFLSMTSA-N 7-[(1s,2s)-2-[2-(3-chlorophenyl)ethenyl]-5-oxocyclopentyl]heptanoic acid Chemical compound C1CC(=O)[C@@H](CCCCCCC(=O)O)[C@@H]1C=CC1=CC=CC(Cl)=C1 GMKMYYJTNINTPO-AEFFLSMTSA-N 0.000 claims description 2
• KTSKAEOSZBYECU-AEFFLSMTSA-N 7-[(1s,2s)-2-[2-(4-fluorophenyl)ethenyl]-5-oxocyclopentyl]heptanoic acid Chemical compound C1CC(=O)[C@@H](CCCCCCC(=O)O)[C@@H]1C=CC1=CC=C(F)C=C1 KTSKAEOSZBYECU-AEFFLSMTSA-N 0.000 claims description 2
• UAARMEMDDVXLNY-QAPCUYQASA-N 7-[(1s,2s)-2-[2-[3,5-bis(trifluoromethyl)phenyl]ethenyl]-5-oxocyclopentyl]heptanoic acid Chemical compound C1CC(=O)[C@@H](CCCCCCC(=O)O)[C@@H]1C=CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 UAARMEMDDVXLNY-QAPCUYQASA-N 0.000 claims description 2
• OQDJZTJTBTYLCA-CVEARBPZSA-N 7-[(1s,2s)-2-[2-[4-chloro-3-(trifluoromethyl)phenyl]ethenyl]-5-oxocyclopentyl]heptanoic acid Chemical compound C1CC(=O)[C@@H](CCCCCCC(=O)O)[C@@H]1C=CC1=CC=C(Cl)C(C(F)(F)F)=C1 OQDJZTJTBTYLCA-CVEARBPZSA-N 0.000 claims description 2
• YQPVSXREBGBXMQ-QAPCUYQASA-N FC(F)(F)C1=CC(C(F)(F)F)=CC(C=C[C@H]2[C@@H](C(=O)CC2)CCCCCCC2=NNN=N2)=C1 Chemical compound FC(F)(F)C1=CC(C(F)(F)F)=CC(C=C[C@H]2[C@@H](C(=O)CC2)CCCCCCC2=NNN=N2)=C1 YQPVSXREBGBXMQ-QAPCUYQASA-N 0.000 claims description 2
• 125000001589 carboacyl group Chemical group 0.000 claims description 2
• SRSPCTBITCTLNX-QUCCMNQESA-N ethyl 7-[(1S,5S)-2-oxo-5-[2-[3-(trifluoromethyl)phenyl]ethenyl]cyclopentyl]heptanoate Chemical compound O=C1[C@H]([C@@H](CC1)C=CC1=CC(=CC=C1)C(F)(F)F)CCCCCCC(=O)OCC SRSPCTBITCTLNX-QUCCMNQESA-N 0.000 claims description 2
• CGGOTNVMGXJPMC-XLIONFOSSA-N ethyl 7-[(1s,2s)-2-[2-(3,5-dichlorophenyl)ethenyl]-5-oxocyclopentyl]heptanoate Chemical compound C1CC(=O)[C@@H](CCCCCCC(=O)OCC)[C@@H]1C=CC1=CC(Cl)=CC(Cl)=C1 CGGOTNVMGXJPMC-XLIONFOSSA-N 0.000 claims description 2
• IMHKMKKKWDPRCR-QUCCMNQESA-N ethyl 7-[(1s,2s)-2-[2-(3-chlorophenyl)ethenyl]-5-oxocyclopentyl]heptanoate Chemical compound C1CC(=O)[C@@H](CCCCCCC(=O)OCC)[C@@H]1C=CC1=CC=CC(Cl)=C1 IMHKMKKKWDPRCR-QUCCMNQESA-N 0.000 claims description 2
• LJRKQYJDVZLMQQ-QUCCMNQESA-N ethyl 7-[(1s,2s)-2-[2-(4-fluorophenyl)ethenyl]-5-oxocyclopentyl]heptanoate Chemical compound C1CC(=O)[C@@H](CCCCCCC(=O)OCC)[C@@H]1C=CC1=CC=C(F)C=C1 LJRKQYJDVZLMQQ-QUCCMNQESA-N 0.000 claims description 2
• KUSJFVWXLUFDFX-XLIONFOSSA-N ethyl 7-[(1s,2s)-2-[2-[3,5-bis(trifluoromethyl)phenyl]ethenyl]-5-oxocyclopentyl]heptanoate Chemical compound C1CC(=O)[C@@H](CCCCCCC(=O)OCC)[C@@H]1C=CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 KUSJFVWXLUFDFX-XLIONFOSSA-N 0.000 claims description 2
• IHBTULXJFPUQQO-MSOLQXFVSA-N ethyl 7-[(1s,2s)-2-[2-[4-chloro-3-(trifluoromethyl)phenyl]ethenyl]-5-oxocyclopentyl]heptanoate Chemical compound C1CC(=O)[C@@H](CCCCCCC(=O)OCC)[C@@H]1C=CC1=CC=C(Cl)C(C(F)(F)F)=C1 IHBTULXJFPUQQO-MSOLQXFVSA-N 0.000 claims description 2
• 238000012423 maintenance Methods 0.000 claims description 2
• 230000009467 reduction Effects 0.000 claims description 2
• 210000001685 thyroid gland Anatomy 0.000 claims description 2
• 125000003396 thiol group Chemical class [H]S* 0.000 claims 5
• 102000018997 Growth Hormone Human genes 0.000 claims 4
• 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims 3
• 229940088597 hormone Drugs 0.000 claims 2
• 239000005556 hormone Substances 0.000 claims 2
• 230000004927 fusion Effects 0.000 claims 1
• 239000003862 glucocorticoid Substances 0.000 claims 1
• 229940037128 systemic glucocorticoids Drugs 0.000 claims 1
• 241000251539 Vertebrata <Metazoa> Species 0.000 description 66
• 206010017076 Fracture Diseases 0.000 description 54
• 229940011871 estrogen Drugs 0.000 description 53
• 239000000262 estrogen Substances 0.000 description 53
• 239000000203 mixture Substances 0.000 description 53
• 239000005557 antagonist Substances 0.000 description 46
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 42
• 241000282412 Homo Species 0.000 description 39
• 241000700159 Rattus Species 0.000 description 34
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